Early and effective cytoreduction for high peripheral white blood cell counts in pediatric patients with acute leukemia may be helpful in preventing complications secondary to hyperviscosity. It also may be a useful adjunct to systemic chemotherapy. As an alternative to automated apheresis for this purpose, manual exchange transfusion is efficacious and does not require hemapheresis instrumentation and disposables and the related special staff. Two patients, a neonate with acute myeloblastic leukemia and a white blood cell count of 422.2 k/microliter as well as a 2 1/2-year-old with an admission diagnosis of acute promyelocytic leukemia and a white blood cell count of 617.4 k/microliter, underwent manual exchange hemotherapy for acute cytoreduction. The procedures were tolerated well, and significant leukocyte removal was achieved, with the respective leukocyte reductions being 81.1 and 68.7%. The techniques available for pediatric cytoreduction are compared, with emphasis on their efficiency and safety and appropriateness for very small children.